Fixed-Bearing Trabecular Metal Total Ankle Arthroplasty Using the Transfibular Approach for End-Stage Ankle Osteoarthritis: An International Non-Designer Multicenter Prospective Cohort Study

This multicenter prospective cohort study assessed the safety and performance of the Trabecular Metal Total Ankle System (TM Ankle; Zimmer) for primary total ankle arthroplasty (TAA).Methods: One hundred and twenty-one consecutive patients qualifying for primary TAA were enrolled in the study. All patients received the TM Ankle implant. Clinical outcome examinations and radiographic evaluations were conducted at 6 weeks, 6 months, 1 year, 2 years, and 3 years. Patient-reported outcome measures (PROMs) were evaluated with use of the EuroQol-5 Dimensions questionnaire (EQ-5D), Ankle Osteoarthritis Scale (AOS), American Orthopaedic Foot & Ankle Society questionnaire (AOFAS), and patient satisfaction at each time point. Complications were classified according to the Canadian Orthopaedic Foot and Ankle Society (COFAS) system.Results: The average AOFAS, EQ-5D, AOS pain, and AOS difficulty scores showed significant improvement at 6 weeks, 6 months, 1 year, 2 years, and 3 years as compared with the preoperative baseline (p Conclusions: The results of the present study indicated that patient well-being significantly increased following TAA with use of the TM Ankle. Radiographic parameters also demonstrated a low incidence of abnormal findings.Level of evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.</p

Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage

Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)–dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.This work was supported by the UK Medical Research MRC (MR/K017047/1) (to S.J.F.), the Computational and Chemical Biology of Stem Cell Niche (MR/L012766/1) (to S.J.F.), the UK Regenerative Medicine Platform (MR/K026666/1) (to S.J.F.), and the Wellcome Trust Institutional Translational Partnership Award (WT iTPA) (to S.F.-G.). J.M.B. was supported by the Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075, and Miguel Servet Program CON14/00129 and CPII19/00008) cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); “Instituto de Salud Carlos III” (CIBERehd), Spain; “Euskadi RIS3” (2019222054 and 2020333010); and the Department of Industry of the Basque Country (Elkartek: KK-2020/00008). This research was funded in whole or in part by The Wellcome Trust (grant number 209710/Z/17/Z), a cOAlition S organization